There is a need for reliable, non-invasive tools to detect, diagnose, characterize, and treat diseased tissues, such as cancer—one of the leading causes of death in the United States. The early detection of disease is necessary for effective therapeutic outcome and is a primary indicator for long term survival. For example, detecting the size and proper boundaries of tumor regions are critical diagnostic problems in medicine. Moreover, demarcating tumor boundaries with high specificity is required to direct therapeutic interventions to tumor location and cause less or no damage to the surrounding healthy tissue. Imaging tools that can also provide therapeutic applications can insure quick treatment and provide for the best healing opportunities.
Current imaging modalities suffer from many drawbacks. Optical imaging, for example, suffers from a shallow penetration depth on the order of millimeters. Additionally, ionizing imaging modalities, such as X-ray, computed tomography, and positron emission tomography, present safety concerns. Furthermore, current technologies employed in cancer treatments cause surrounding healthy tissue damage along with tumor necrosis, and such treatments require separate applications and multiple visits.
Biological processes that lead to disease may occur at the molecular level. Nanotechnology offers unprecedented access to the machinery of living cells, and therefore provides the opportunity to study and interact with normal and cancerous cells in real time, at the molecular and cellular scales, and during the earliest stages of the cancer process. Studies have shown gold nanoparticles can be functionalized with antibodies to specifically bind to molecular markers that are indicative of highly proliferative cells. Furthermore, antibodies can target receptors that are overexpressed on the surface of different types of cancerous cells.
Photoacoustic imaging is a technique that can provide functional information based on differences in optical absorption properties of the tissue constituents. The absorption of electromagnetic energy, such as light, and the subsequent emission of an acoustic wave by the tissue is the premise of photoacoustic imaging. Specifically for photoacoustic imaging, the tissue is irradiated with nanosecond pulses of low energy laser light. Broadband ultrasonic acoustic waves may be generated within the irradiated volume; the tissue absorbs the light and then undergoes rapid thermoelastic expansion. An ultrasound transducer and associated receiver electronics may be used to acquire the photoacoustic signal.
Photoacoustic signal can be generated through four mechanisms including thermal (also referred as thermoelastic) expansion, vaporization, photochemical processes, and optical breakdown. However, in biomedical applications of photoacoustic imaging and sensing, the only biologically safe mechanism to date is thermal expansion. Unfortunately, thermal expansion is one of the least efficient mechanisms of light-sound energy conversion and produces acoustic waves of relatively low amplitude. In thermal expansion-based photoacoustic imaging, sufficiently short laser pulses are absorbed by tissue chromophores, causing localized volume heating, leading to rapid expansion and generation of acoustic pressure waves. With the exception of melanin, hemoglobin, and other porphyrins, tissue components have relatively low optical absorption properties, limiting the overall endogenous contrast in photoacoustic imaging.
Current technologies for ultrasound and photoacoustic imaging utilize contrast agents, such as acoustic droplets and metal nanoparticles, respectively. The metal nanoparticles typically range between about 1-about 100 nanometers, while the ultrasound contrast agents have diameters on the order of micrometers. Consequently, current ultrasound contrast agents are too large and/or bulky to be useful in passive diffusion into tumor tissues, for cellular imaging, or to pass through small capillaries and reach certain diseased sites.